Isoforms of the Papillomavirus Major Capsid Protein Differ in Their Ability to Block Viral Spread and Tumor Formation

Frontiers in Immunology

Gabriele Schmidt¹  Daniel Hasche²  Ilona Braspenning-Wesch²  Frank Rösl²  Rui Cao²  Melinda Ahmels²  Sonja Stephan²  Martin Müller³ 

[1] Core Facility Unit Light Microscopy, German Cancer Research Center (DKFZ), Heidelberg, Germany;Division of Viral Transformation Mechanisms, Research Program “Infection, Inflammation and Cancer”, German Cancer Research Center (DKFZ), Heidelberg, Germany;Research Group Tumorvirus-specific Vaccination Strategies, Research Program “Infection, Inflammation and Cancer”, German Cancer Research Center (DKFZ), Heidelberg, Germany;

关键词: immune escape mechanism;    vaccination;    cutaneous papillomaviruses;    Mastomys coucha;    neutralizing antibodies;    major capsid protein (L1);   

DOI  :  10.3389/fimmu.2022.811094

来源: DOAJ

【 摘 要 】

Notably, the majority of papillomaviruses associated with a high cancer risk have the potential to translate different isoforms of the L1 major capsid protein. In an infection model, the cutaneous Mastomys natalensis papillomavirus (MnPV) circumvents the humoral immune response of its natural host by first expressing a 30 amino acid extended L1 isoform (L1LONG). Although inducing a robust seroconversion, the raised antibodies are not neutralizing in vitro. In contrast, neutralizing antibodies induced by the capsid-forming isoform (L1SHORT) appear delayed by several months. We now provide evidence that, although L1LONG vaccination showed a strong seroconversion, these antibodies were not protective. As a consequence, virus-free animals subsequently infected with MnPV still accumulated high numbers of transcriptionally active viral genomes, ultimately leading to skin tumor formation. In contrast, vaccination with L1SHORT was completely protective. This shows that papillomavirus L1LONG expression is a unique strategy to escape from antiviral immune surveillance.

【 授权许可】

Unknown